Etiology and pathogenesis of human brain tumors are unknown. The high incidence of brain tumors in rats following single or multiple extraneural applications of N-Nitroso compounds suggests that brain tumors in man may be induced by a single pre-or postnatal contact with extrinsic or intrinsic neurooncogenic agents. Since N-Nitroso compounds occur in nature and human contact with these substances is likely, it is proposed to use these specific neurooncogenic agents as a model for the investigation of the induction phase of brain neoplasms. The molecular- chemical interactions of these compounds and their catabolites with cellular components will be investigated. The model will be used to study immune mechanisms of brain tumors with the ultimate goal to develop a natural approach toward immune therapy. It will also be investigated whether the direct interactions of these compounds with the cellular genetic apparatus is solely responsible for neoplastic transformation or whether the effect of these compounds is a result of activation of a tumor virus or depression of the hypothetical on cogenes.